Submissions for variant NM_001447.3(FAT2):c.59A>G (p.Lys20Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003121821	SCV003788996	uncertain significance	not provided	2022-10-05	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 20 of the FAT2 protein (p.Lys20Arg). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with FAT2-related conditions. This variant is present in population databases (rs766681033, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant.
CeGaT Center for Human Genetics Tuebingen	RCV003121821	SCV004157875	benign	not provided	2022-08-01	criteria provided, single submitter	clinical testing	FAT2: BS1, BS2